No abstract

Human papillomavirus (HPV)-related multiphenotypic sinonasal carcinoma (HMSC) is a recently described distinctive clinicopathologic entity defined by association to high risk HPV, localization to sinonasal tract and close histologic resemblance to salivary gland tumors. Lack of awareness of its pathologic features and biology among pathologists and oncologists make this entity susceptible to misdiagnosis and erroneous management. Herein, we illustrate a case of HMSC of the nasal cavity associated with heretofore unreported subtype HPV-52 and discuss the challenges associated with diagnosis and management of this rare tumor. A 48-year-old woman with intermittent epistaxis for 6 months presented with a nasal mass and underwent middle turbinectomy. Histology showed a tumor with features typical of adenoid cystic carcinoma (ACC) in the form of basaloid cells and cribriform architecture. However, careful inspection revealed findings uncommon in ACC; such as surface pagetoid tumor spread, areas of solid sheets of myoepithelial cells accompanied by increased mitotic figures which prompted immunohistochemistry. Multidirectional differentiation into ductal (CK7, AE1/AE3) and myoepithelial (p63, p40, S100, calponin) lineage together with strong and diffuse immunopositivity for p16 distinguished this tumor from ACC. HPV genotyping was positive for high risk HPV subtype HPV52, which confirmed the diagnosis of HMSC. HPV-related multiphenotypic sinonasal carcinoma is an under-recognized unique clinicopathologic entity that needs awareness to avoid mistaking it for commoner salivary gland tumors. Making accurate diagnosis of this newly-described tumor is imperative in order to understand its biology and to develop optimal therapeutic strategies.

Multiple Myeloma(MM) is genetically complex and heterogeneous neoplasm in which cytogenetics is major genetic factor which plays an important role in the risk stratification of disease. High risk MM based upon cytogenetic classification includes primary IGH translocations t(4;14), t(14;16), t(14;20), and secondary progressive aberrations such as gain/Amp(1q) , 1p deletion , del(17p) & hypodiploidy. Several studies have proved that interphase FISH can efficiently detect primary as well as secondary cryptic aberrations very efficiently in lowest 5%- 10% abnormal plasma cells population. Present large scale study was undertaken to evaluate the incidence of cytogenetic abnormalities , to analyse the correlation of conventional karyotyping with FISH and to seek the geographic heterogeinity in the incidence of primary as well as secondary aberrations in our Indian vs Western population. We conducted prospective studies of 1104 patients consecutively referred from the primary, secondary and tertiary oncology centres from all over India. Interphase FISH was performed on isolated plasma cells. karyotype analysis was done as per ISCN, 2016,2020. In present large scale studies from India, FISH could detect cytogenetic abnormalities in 67.6% cases with an incidence of 59% non-hyperdiploidy(NHD). The incidence of IGH translocation was 26% vs literature frequency of 40%-50% which was mainly affected by low incidence 6% of t(11;14) in contrast to 15-20% in other series. Additionally, the association of secondary progressive aberrations in hyperdiploid (HD)group than non-hyperdiploid group in our patients is not a common finding . A biallelic inactivation of TP53 as an ultra-high risk factor was detected in old-aged patients. These observations disclose the novel findings and strongly indicate the racial disparity which leads to geographic heterogeneity. In contrast to FISH, conventional karyotyping could detect MM-related aberrations in 50% cases , of which 44% revealed highly complex karyotype with common aberrations of chromosome 1q. Overall FISH was found to be novel , easy approach with high success rate and capability of detection of all cytogenetic abnormalities that add valid information for the risk stratification of disease which in future in combination with mutation profile and Gene expression profile will help in further refinement of disease & identification of actionable targets.

Background: The present study aims to comprehensively analyze expression of Activin signaling components in oral cancer and to determine the predominant Activin expressed and its influence on prognosis. As our preliminary studies indicated regulation of Activin gene by p63, we also propose to assess its correlation with p63/ p53 in oral tumors and its impact on outcome. Methods: Expression of Activin subunits, receptors, and regulators was assessed by qRT-PCR and Western blotting. Correlation between Activin A and p63/p53 expression was evaluated in oral tumors by immunohistochemistry and their association with clinical outcome was determined by Kaplan-Meier curves and Cox regression. Results: Activin βA transcripts were upregulated (P = .013) in oral dysplastic and cancer cells compared with normal oral mucosa. Expression of Activin receptors and regulators was also altered. Activin βA protein was significantly upregulated in oral tumors and adjacent normal tissues compared with normal oral mucosa (P < .0001). Expression of Activin βA and p63 significantly correlated in oral tumors, correlation being stronger in tumors with high p53 (r = −.394, P = .005). Activin βA overexpression was associated with advanced tumor stage (P = .021), positive nodes (P = .045), poor recurrence-free survival (P = .013), and overall survival (P = .024), while its concomitant overexpression with p63 was a better predictor of recurrence-free survival